Part 9 Acute Coronary Syndromes

Part 9: Acute Coronary Syndromes
2015 American Heart Association Guidelines Update for Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care
Robert E. O’Connor, Chair; Abdulaziz S. Al Ali; William J. Brady; Chris A. Ghaemmaghami;
Venu Menon; Michelle Welsford; Michael Shuster
Introduction
Clinicians often struggle with uncertainty and complexity in
deciding which course of treatment will likely lead to an optimal outcome for an individual patient. Scientific research provides information on how patient populations have responded
to treatment regimens, and this information, combined with a
knowledge of the individual patient, can help guide the clinician’s decisions.
The recommendations in this 2015 American Heart
Association (AHA) Guidelines Update for Cardiopulmonary
Resuscitation (CPR) and Emergency Cardiovascular Care
(ECC) are based on an extensive evidence review process
that was begun by the International Liaison Committee
on Resuscitation (ILCOR) after the publication of the
ILCOR 2010 International Consensus on Cardiopulmonary
Resuscitation and Emergency Cardiovascular Care Science
With Treatment Recommendations1,2 and was completed in
February 2015.3,4
In this in-depth evidence review process, ILCOR examined topics and then generated a prioritized list of questions
for systematic review. Questions were first formulated in
PICO (population, intervention, comparator, outcome) format,5 and then a search for relevant articles was performed.
The evidence was evaluated by the ILCOR task forces by
using the standardized methodologic approach proposed by
the Grading of Recommendations Assessment, Development
and Evaluation (GRADE) Working Group.6
The quality of the evidence was categorized based on the
study methodologies and the 5 core GRADE domains of risk
of bias, inconsistency, indirectness, imprecision, and other
considerations (including publication bias). Then, where
possible, consensus-based treatment recommendations were
created.
To create this 2015 AHA Guidelines Update for CPR and
ECC, the AHA formed 15 writing groups, with careful attention to avoid conflicts of interest, to assess the ILCOR treatment
recommendations, and to write AHA treatment recommendations by using the AHA Class of Recommendation and Level
of Evidence (LOE) system. The recommendations made in the
2015 Guidelines Update for CPR and ECC are informed by the

ILCOR recommendations and GRADE classification, in the
context of the delivery of medical care in North America. In
the online version of this publication, live links are provided so
the reader can connect directly to the systematic reviews on the
Scientific Evidence Evaluation and Review System (SEERS)
website. These links are indicated by a superscript combination of letters and numbers (eg, ACS 873).
This 2015 Guidelines Update offers recommendations for
the care of patients with acute coronary syndromes (ACS).
The recommendations made here update those made in the
2010 Guidelines and address only those issues that were
reviewed in 2015. The ILCOR ACS Task Force did not review
areas in which it found a paucity of new evidence between
2010 and 2015; therefore, the 2010 Guidelines for these unreviewed areas remain current. For example, acetylsalicylic acid
administration has been shown to be of benefit in ACS and
was recommended by the 2010 Guidelines.7 Acetylsalicylic
acid was not reviewed by the ACS Task Force in 2015, so the
recommendations from 2010 should be used. (Note: The First
Aid section of this 2015 Guidelines Update makes recommendations on acetylsalicylic acid administration by nonmedical
personnel—see “Part 15: First Aid”). The recommendations
that were not reviewed in 2015 will either be reviewed and
included in future AHA Guidelines for CPR and ECC or will
be in the most recent ACC/AHA Guidelines.8–10
A table of recommendations made in this update, as well
as the recommendations made in “Part 10: Acute Coronary
Syndromes” of the 2010 Guidelines,7 can be found in the
Appendix.
The 2015 Guidelines for ACS are directed toward practitioners who provide care for patients with suspected ACS
from the time of first medical contact until disposition from
the emergency department (ED). Care providers during this
time may include emergency medical service (EMS) dispatchers, first responders, EMT-Bs, paramedics, nurses, physicians,
and other independent practitioners.

Methodology
ILCOR performed 18 systematic reviews (14 based on
meta-analyses) on more than 110 relevant studies that span

The American Heart Association requests that this document be cited as follows: O’Connor RE, Al Ali AS, Brady WJ, Ghaemmaghami CA, Menon V,
Welsford M, Shuster M. Part 9: acute coronary syndromes: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and
Emergency Cardiovascular Care. Circulation. 2015;132(suppl 2):S483–S500.
(Circulation. 2015;132[suppl 2]:S483–S500. DOI: 10.1161/CIR.0000000000000263.)
© 2015 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org

DOI: 10.1161/CIR.0000000000000263

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S484  Circulation  November 3, 2015
40 years. Based on these reviews, the ACS Writing Group
assessed the evidence and assigned an LOE by using AHA
definitions. The LOE for a given intervention supports the
class or “strength” of recommendation that the writing
group assigned. This update uses the newest AHA Class
of Recommendation and LOE classification system, which
contains modifications to the Class III recommendation and
introduces LOE B-R (randomized studies) and B-NR (nonrandomized studies), as well as LOE C-LD (limited data) and
LOE C-EO (consensus of expert opinion). For further information, see “Part 2: Evidence Evaluation and Management
of Conflicts of Interest.”

Diagnostic Interventions in ACS
Prehospital ECG and Prehospital STEMI
Activation of the Catheterization
LaboratoryACS 873, ACS 336
Prehospital acquisition of 12-lead electrocardiograms (ECGs)
has been recommended by the AHA Guidelines for CPR
and Emergency Cardiovascular Care since 2000. The 2015
ILCOR systematic review examined whether acquisition of a
prehospital ECG with transmission of the ECG to the hospital, notification of the hospital of the need for fibrinolysis, or
activation of the catheterization laboratory changes any major
outcome.
2015 Evidence Summary
Obtaining an ECG early in the assessment of patients with
possible ACS ensures that dynamic ECG changes suggestive
of cardiac ischemia and ACS will be identified, even if they
normalize before initial treatment.11
An early ECG may also enable ST elevation myocardial
infarction (STEMI) to be recognized earlier. Acquiring a prehospital ECG and determining the presence of STEMI effectively makes the prehospital provider the first medical contact.
The prehospital ECG can reliably enable identification of
STEMI before arrival at the hospital,12 but if notification of
the receiving facility does not occur, any benefit to prehospital
STEMI recognition is lost.
Prehospital ECG acquisition coupled with hospital notification if STEMI is identified consistently reduces the time to
reperfusion in-hospital (first medical contact–to–balloon time,
first medical contact–to–needle time, door-to-balloon time,
door-to-needle time).13 To reduce time to STEMI reperfusion
in-hospital, rapid transport and early treatment must occur in
parallel with hospital preparation for the arriving patient.
Prehospital ECGs reduce the time to reperfusion with
fibrinolytic therapy and also reduce the time to primary percutaneous coronary intervention (PPCI) and facilitate triage of
STEMI patients to specific hospitals.4 Prehospital activation of
the catheterization laboratory (as opposed to delaying cardiac
catheterization laboratory activation until the patient arrives at
the hospital) is independently associated with improved times
to PPCI and reduced mortality.4
Prehospital ECG acquisition and hospital notification
reduce mortality by 32% when PPCI is the reperfusion
strategy (benefit is accentuated when prehospital activation
occurs) and by 24% when ED fibrinolysis is the reperfusion
strategy.4

2015 Recommendations—Updated
Prehospital 12-lead ECG should be acquired early for patients
with possible ACS (Class I, LOE B-NR).
Prehospital notification of the receiving hospital (if fibrinolysis is the likely reperfusion strategy) and/or prehospital
activation of the catheterization laboratory should occur for all
patients with a recognized STEMI on prehospital ECG (Class
I, LOE B-NR).

Computer-Assisted ECG STEMI InterpretationACS 559
The identification of STEMI in patients with suspected
STEMI is often made on clinical grounds in combination with
ECG findings as interpreted by a physician. The 2015 ILCOR
systematic review addressed whether computer-assisted ECG
interpretation improves identification of STEMI while minimizing unnecessary intervention.
2015 Evidence Summary
Studies examined both underdiagnosis (false-negative results)
and overdiagnosis (false-positive results)14,15 or overdiagnosis
alone16–20 by computer ECG interpretation. There was wide
variation in the proportion of false-positive results (0% to
42%) and of false-negative results (22% to 42%).
These variations in accuracy seemed to occur because different ECG machines use different algorithms and because
the computer interpretations are compared variously with
interpretation by cardiologists, emergency physicians, and
discharge diagnosis of STEMI. Moreover, the sensitivity and
specificity of the test will differ depending on the prevalence
of STEMI.
Both studies that examined false-negative results suggest
that computer interpretation of ECG tracing produces unacceptably high rates of false-negative results in the identification
of STEMI. A few studies show that computer interpretation
can produce an unacceptably high rate of false-positive diagnoses. Interpretation by trained personnel in conjunction with
computer interpretation may lower the rate of false results
obtained when using computer interpretation alone.
2015 Recommendations—New
Because of high false-negative rates, we recommend that
computer-assisted ECG interpretation not be used as a sole
means to diagnose STEMI (Class III: Harm, LOE B-NR).
We recommend that computer-assisted ECG interpretation
may be used in conjunction with physician or trained provider
interpretation to recognize STEMI (Class IIb, LOE C-LD).

Nonphysician STEMI ECG InterpretationACS 884
When physicians are not present or not available to interpret
an ECG, other methods for interpretation must be used so
that timely patient care is not adversely affected. The 2015
ILCOR systematic review examined whether nonphysicians
such as paramedics and nurses could identify STEMI on an
ECG so that earlier identification of STEMI could be made
with acceptable rates of either underdiagnosis (false-negative
results) or overdiagnosis (false-positive results).
2015 Evidence Summary
Three observational studies compared the diagnostic accuracy
of the interpretation of ECGs as either STEMI or No STEMI

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O’Connor et al   Part 9: Acute Coronary Syndromes   S485
by physicians and paramedics.21–23 While the studies used different methods to adjudicate the diagnosis, including World
Health Organization criteria,21 discharge diagnosis,22 and catheterization laboratory activation,23 all 3 studies showed a fairly
high rate of agreement between physician and paramedic rates
of distinguishing STEMI from No STEMI.
Overidentification of STEMI may have a significant
adverse effect on resource utilization. An additional 6 studies examined the accuracy of paramedic identification of
STEMI and reported false-positive rates (patients incorrectly
diagnosed with STEMI by paramedics when no STEMI was
present) ranging from 8% to 40%.17,24–28 One study reported
that transmission of the ECG to the ED for emergency physician interpretation, compared with paramedic interpretation
alone, improves the positive predictive value of the prehospital 12-lead ECG for triage and therapeutic decision making.24
The time from hospital arrival to percutaneous coronary intervention (PCI) with balloon inflation was significantly shorter
if EMS activated the catheterization laboratory than if the
laboratory was activated by hospital staff25,26,28 or if the patient
was directly admitted to the catheterization laboratory.27
2015 Recommendation—New
While transmission of the prehospital ECG to the ED physician may improve positive predictive value (PPV) and
therapeutic decision-making regarding adult patients with
suspected STEMI, if transmission is not performed, it may be
reasonable for trained nonphysician ECG interpretation to be
used as the basis for decision-making, including activation of
the catheterization laboratory, administration of fibrinolysis,
and selection of destination hospital (Class IIa, LOE B-NR).

Biomarkers in ACSACS 737
Cardiac troponin measurement, along with the ECG, is an
integral part of the evaluation of patients with signs and
symptoms suspicious for ACS. The detection of an elevated
troponin (Tn) above the 99th percentile upper reference
limit is highly sensitive and specific for myocardial necrosis, and is required in the universal definition of myocardial
infarction (MI).29
Contemporary troponin assays are termed “high-sensitivity” (hs) if they are able to detect measurable troponin levels even in healthy individuals, with a threshold of detection
of 0.006 ng/ml for hs-cTnI and 0.005 for hs-cTnT. Positive
results are an order of magnitude higher than the threshold
for detection and are usually defined as exceeding the 99th
percentile of values with a coefficient of variation of less
than 10%.30
More than 8 million patients are evaluated for potential ischemic chest pain in US EDs each year, with troponin
measurement serving as one of the crucial diagnostic tests.31
Because of this vast number of patients with potential ischemic
chest pain, it is highly desirable to find some combination of
diagnostic testing that can reliably identify patients who are
not experiencing ischemia and can be safely discharged from
the ED.
The 2015 ILCOR systematic review examined whether
a negative troponin test could be used to identify patients at
low risk for ACS when they did not have signs of STEMI,

ischemia, or changes on the ECG that could mask signs of
acute ischemia or MI.
The clinician should bear in mind that unstable angina can
present without any objective data of myocardial ischemic
injury (ie, with normal ECG and normal troponin), in which
case the initial diagnosis depends solely on the patient’s clinical history and the clinician’s interpretation and judgment.
2015 Evidence Summary
Two observational studies used troponin (cTnI, cTnT, or hscTnT) measured at 0 and 2 hours to assess whether patients
could be safely discharged from the ED.32,33 In these studies,
2.5% to 7.8% of patients with ACS had (false-) negative tests.
That is, ACS would have been missed in 2.5% to 7.8% of the
patients studied. With an unstructured risk assessment used in
addition to the troponin testing, 2.3% of patients identified as
being at low risk have a major adverse cardiac event (MACE)
on 30-day follow-up. A formal risk assessment instrument
was not used in either of these 2 studies.
Six additional observational studies combined troponin
testing (using cTnI, cTnT, hs-cTnI, or hs-cTnT) with use
of clinical decision rules such as TIMI, Vancouver, North
American, or HEART. The proportion of false-negative
results among patients with 30-day MACE ranged from 0%
to 1.2%.34–39 When the age cutoff for low-risk patients was
increased from 50 years to 60 years for the North American
Chest Pain Rule, the proportion of false-negative results rose
from 0% to 1.1%.37 Because the rules were used in combination with different troponin measurements, and each test identified 99% of patients with ACS as defined by 30-day MACE,
it was difficult to directly compare rule or assay performance.
One study36 identified 1 additional ACS patient by using the
Vancouver rule when the hs-cTnI was used instead of the cTnI.
2015 Recommendations—New
We recommend against using hs-cTnT and cTnI alone measured at 0 and 2 hours (without performing clinical risk stratification) to identify patients at low risk for ACS (Class III:
Harm, LOE B-NR).
We recommend that hs-cTnI measurements that are less
than the 99th percentile, measured at 0 and 2 hours, may be
used together with low-risk stratification (TIMI score of 0 or
1 or low risk per Vancouver rule) to predict a less than 1%
chance of 30-day MACE (Class IIa, LOE B-NR).
We recommend that negative cTnI or cTnT measurements
at 0 and between 3 and 6 hours may be used together with
very low-risk stratification (TIMI score of 0, low-risk score
per Vancouver rule, North American Chest Pain score of 0 and
age less than 50 years, or low-risk HEART score) to predict a
less than 1% chance of 30-day MACE (Class IIa, LOE B-NR).

Therapeutic Interventions in ACS
ADP Inhibition: Adjunctive Therapy in Patients
With Suspected STEMI—ADP InhibitorsACS 335
The 2015 ILCOR systematic review addressed the clinical
impact of the timing of administration of adenosine diphosphate (ADP) inhibition in the treatment of patients with
suspected STEMI. The relative merit of early prehospital as
compared with hospital administration of ADP inhibition as a

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general treatment strategy was assessed. Differences between
individual ADP inhibitors were not examined.
The preferred reperfusion strategy for patients with
STEMI is identification and restoration of normal flow in the
infarct-related artery using primary percutaneous intervention. The use of potent dual antiplatelet therapy in STEMI
patients undergoing PPCI is associated with improved clinical
outcomes as well as lower rates of acute stent thrombosis.40,41
Given the short time from first medical contact to balloon
inflation, treatment with oral ADP inhibitors in a prehospital setting has the potential to enhance platelet inhibition and
improve procedural and clinical outcomes after PCI.
2015 Evidence Summary
Three randomized controlled trials (RCTs)42–44 showed no
additional benefit to the outcome of 30-day mortality and no
additional benefit or harm with respect to major bleeding with
prehospital administration compared with in-hospital administration of an ADP-receptor antagonist.
2015 Recommendation—New
In patients with suspected STEMI intending to undergo PPCI,
initiation of ADP inhibition may be reasonable in either the
prehospital or in-hospital setting (Class IIb, LOE C-LD).

Prehospital Anticoagulants Versus None in
STEMIACS 562
In patients with suspected STEMI, anticoagulation is standard treatment recommended by the American College
of Cardiology Foundation/AHA Guidelines.9,10 The 2015
ILCOR systematic review sought to determine if any important outcome measure was affected if an anticoagulant was
administered prehospital compared with whether that same
anticoagulant was administered in-hospital.
2015 Evidence Summary
A single nonrandomized, case-control study found that while
flow rates were higher in an infarct-related artery when heparin and aspirin were administered in the prehospital setting
versus the ED, there was no significant difference in death,
PCI success rate, major bleeding, or stroke.45
2015 Recommendations—New
While there seems to be neither benefit nor harm to administering heparin to patients with suspected STEMI before their
arrival at the hospital, prehospital administration of medication adds complexity to patient care. We recommend that EMS
systems that do not currently administer heparin to suspected
STEMI patients do not add this treatment, whereas those that
do administer it may continue their current practice (Class IIb,
LOE B-NR).
In suspected STEMI patients for whom there is a planned
PPCI reperfusion strategy, administration of unfractionated
heparin (UFH) can occur either in the prehospital or in-hospital setting (Class IIb, LOE B-NR).

Prehospital Anticoagulation for STEMIACS 568
The 2015 ILCOR systematic review examined whether the
prehospital administration of an anticoagulant such as bivalirudin, dalteparin, enoxaparin, or fondaparinux instead of UFH,

in suspected STEMI patients who are transferred for PPCI,
changes any major outcome.
2015 Evidence Summary
One RCT provided evidence in patients transferred for PCI
for STEMI that there was no significant difference between
prehospital bivalirudin compared with prehospital UFH with
respect to 30-day mortality, stroke, or reinfarction. However,
this same study did demonstrate a decreased incidence of
major bleeding with bivalirudin.46 Another study (this one a
non-RCT) also demonstrated no difference between prehospital bivalirudin compared with prehospital UFH with respect
to 30-day mortality, stroke, and reinfarction. In contrast to the
RCT, this study did not find a difference in major bleeding.47
Although stent thrombosis was not considered as an a priori outcome, bivalirudin was strongly associated with the risk
of acute stent thrombosis (relative risk, 6.11; 95% confidence
interval, 1.37–27.24).46 Such association is also consistently
reported in other published in-hospital studies and meta-analyses of this agent in patients undergoing PCI.48–50 While the
benefit of bivalirudin over UFH alone in reducing bleeding
complications has been shown, this benefit may be offset by
the risk of stent thrombosis.
We have identified 1 RCT51 enrolling 910 patients transferred for PPCI for STEMI that showed no significant difference between prehospital enoxaparin compared with
prehospital UFH with respect to 30-day mortality, stroke,
reinfarction, or major bleeding.
It is important to consider the results of the comparison
between anticoagulants given in prehospital versus in-hospital
settings in STEMI patients. Only UFH has been evaluated
directly in this setting, and because there is no clear evidence
of benefit, we are not recommending that EMS systems implement anticoagulant administration in the prehospital setting.
2015 Recommendations—New
It may be reasonable to consider the prehospital administration of UFH in STEMI patients or the prehospital administration of bivalirudin in STEMI patients who are at increased risk
of bleeding (Class IIb, LOE B-R).
In systems in which UFH is currently administered in the
prehospital setting for patients with suspected STEMI who are
being transferred for PPCI, it is reasonable to consider prehospital administration of enoxaparin as an alternative to UFH
(Class IIa, LOE B-R).

Routine Supplementary Oxygen Therapy in
Patients Suspected of ACSACS 887
The 2010 AHA Guidelines for CPR and ECC noted that there
was insufficient evidence to recommend the routine use of
oxygen therapy in patients who had an uncomplicated ACS
without signs of hypoxemia or heart failure and that older literature suggested harm with supplementary oxygen administration in uncomplicated ACS without demonstrated need for
supplementary oxygen.52,53 The 2010 Guidelines, however,
did recommend that oxygen be administered to patients with
breathlessness, signs of heart failure, shock, or an oxygen saturation less than 94%.7
In 2015, the ILCOR systematic review specifically
addressed the use of oxygen as an adjunctive medication in the

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O’Connor et al   Part 9: Acute Coronary Syndromes   S487
treatment of patients who had normal oxygen saturation but
had suspected ACS. The 2 treatment approaches (either providing or withholding oxygen) were compared with respect
to outcomes: rate of death, infarction size, resolution of chest
pain, and ECG abnormality resolution. The new recommendation in this 2015 Guidelines Update applies only to the use of
oxygen for patients suspected of ACS who have normal oxygen saturations.

Adjunctive Therapy in Patients Suspected of ACS:
Oxygen
Respiratory compromise, manifested by oxygen desaturation,
can occur during ACS, most often as a result of either acute pulmonary edema or chronic pulmonary disease. Supplementary
oxygen has previously been considered standard therapy for
the patient suspected of ACS, even in patients with normal
oxygen saturation. The rationale for oxygen therapy was a
belief that maximization of oxygen saturation may improve
delivery of oxygen to the tissues and thus reduce the ischemic process and related negative outcomes. In other patient
groups, such as resuscitated cardiac arrest patients, hyperoxia
has been associated with worse outcomes as compared with
normoxia.54–56
2015 Evidence Summary
There is limited evidence regarding the use of supplementary
oxygen therapy in suspected ACS patients with normal oxygen saturation. The practice of administering oxygen to all
patients regardless of their oxygen saturation is based on both
rational conjecture and research performed before the current
reperfusion era in acute cardiac care.52 More recent study of
this issue is also limited,57,58 although 2 trials addressing this
question are in progress or are recently completed. The AVOID
trial,59 a multicentered prospective RCT published since the
2015 ILCOR systematic review, compared oxygen administration with no oxygen administration in suspected STEMI
patients without respiratory compromise. When oxygen was
administered, the patients experienced increased myocardial
injury at presentation and larger infarction size at 6 months.
Reinfarction and the incidence of cardiac arrhythmias were
also increased in the oxygen therapy group.59 Because this
study was published after the ILCOR systematic review, it
was not considered in our treatment recommendation.
There is no evidence that withholding supplementary oxygen therapy in normoxic patients suspected of ACS affects the
rate of death and/or resolution of chest pain; there is only a
very low level of evidence that withholding supplementary
oxygen reduces infarction size, and there is no evidence that
withholding supplementary oxygen therapy affects the resolution of ECG abnormality.52,53,57,58
2015 Recommendation—Updated
The provision of supplementary oxygen to patients with suspected ACS who are normoxic has not been shown to reduce
mortality or hasten the resolution of chest pain. Withholding
supplementary oxygen in these patients has been shown to
minimally reduce infarct size.
The usefulness of supplementary oxygen therapy has not
been established in normoxic patients. In the prehospital,
ED, and hospital settings, the withholding of supplementary

oxygen therapy in normoxic patients with suspected or confirmed acute coronary syndrome may be considered (Class
IIb, LOE C-LD).

Reperfusion Decisions in
STEMI Patients
The 2010 ILCOR systematic review addressed the use of
reperfusion therapy, including fibrinolysis and PPCI, in
patients with STEMI who present initially to non–PCI-capable hospitals. The 2015 AHA Guidelines Update for CPR and
ECC examines the most appropriate reperfusion therapy in
STEMI patients presenting to non–PCI-capable hospitals as
well as the need for hospital transfer for PCI, or ischemiaguided (ie, rescue) coronary angiography and/or PCI.

Prehospital Fibrinolysis, Hospital Fibrinolysis, and
Prehospital Triage to PCI CenterACS 338, ACS 341
Prehospital fibrinolysis requires a sophisticated system of
provider expertise, well-established protocols, comprehensive
training programs, medical oversight, and quality assurance.4
In many European systems, a physician provides prehospital fibrinolysis, but nonphysicians can also safely administer
fibrinolytics.60 The 2015 ILCOR systematic review evaluated
whether prehospital fibrinolysis is preferred to reperfusion inhospital where the prehospital fibrinolysis expertise, education, and system support exists.
2015 Evidence Summary
Prehospital fibrinolysis will achieve earlier treatment as compared with ED fibrinolysis. Where transport times are more
than 30 to 60 minutes, the time advantage conferred by prehospital fibrinolysis provides a mortality benefit.4 This benefit from prehospital fibrinolysis was found consistently by 3
RCTs performed more than 20 years ago.61–63 However, these
studies were performed at a time when hospital fibrinolytic
administration typically took well in excess of 60 minutes. It
is not clear the extent to which that mortality benefit would be
maintained today when the hospital time to fibrinolytic treatment is typically considerably shorter than it was 20 years
ago. The only recent evidence for this therapy comes from a
non-RCT that confirms a small mortality benefit to prehospital
fibrinolysis.64 When transport times are shorter than 30 to 60
minutes, the mortality benefit from administering fibrinolytics
before hospital arrival may be lost and may no longer outweigh the relative complexity of providing this therapy outside of a hospital.
However, PPCI is generally preferred to in-hospital fibrinolysis for STEMI reperfusion.65 Prehospital providers can
transport STEMI patients directly to PCI centers, and activation of the team before arrival allows the team to assemble and
prepare in parallel with transport. Several studies in the past
15 years have compared transport directly for PPCI with prehospital fibrinolysis and found no mortality benefit of either
therapy, although the relatively rare harm from intracranial
hemorrhage is greater with fibrinolysis.66–69
2015 Recommendations—Updated
Where prehospital fibrinolysis is available as part of a STEMI
system of care, and in-hospital fibrinolysis is the alternative
treatment strategy, it is reasonable to administer prehospital

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fibrinolysis when transport times are more than 30 minutes
(Class IIa, LOE B-R).
Where prehospital fibrinolysis is available as part of the
STEMI system of care and direct transport to a PCI center
is available, prehospital triage and transport directly to a PCI
center may be preferred because of the small relative decrease
in the incidence of intracranial hemorrhage without evidence
of mortality benefit to either therapy (Class IIb, LOE B-R).

ED Fibrinolysis and Immediate PCI Versus
Immediate PCI AloneACS 882
Delays in the performance of PPCI are commonly observed
in clinical practice. In many regions, the delay arises because
of the relative paucity of dedicated PPCI centers, resulting in
the need for prolonged transfer times. In this context, combining the availability and ease of administration of fibrinolytic
with the downstream certainty of mechanical reperfusion with
facilitated PCI was an attractive concept, with its promise of
both restoring early flow to the infarct-related artery while
addressing the concerns of pharmacologic failure and need for
rescue. This was counterbalanced by the concern for a heightened risk of bleeding complications and detrimental procedural outcomes in this prothrombotic milieu.
The 2015 ILCOR systematic review addressed the merits
for reperfusion in STEMI patients with a strategy of initial
fibrinolysis followed by immediate PCI versus immediate PCI
alone.
2015 Evidence Summary
A number of randomized clinical trials have addressed clinical
outcomes after initial treatment with a half- or full-dose fibrinolytic agent followed by dedicated immediate PCI compared
with immediate PCI alone.
The studies showed no benefit to mortality,70–74 nonfatal
70–74
or target vessel revascularization70–73 when fibrinolytic
MI,
administration is combined with immediate PCI as compared
with immediate PCI alone.
The studies did, however, identify harm from intracranial hemorrhage70–72 or major bleeding70–74 when fibrinolytic
administration is combined with immediate PCI versus immediate PCI alone.
2015 Recommendation—New
In the treatment of patients with suspected STEMI, the combined application of fibrinolytic therapy followed by immediate PCI (as contrasted with immediate PCI alone) is not
recommended (Class III: Harm, LOE B-R).

Delayed PCI Versus Fibrinolysis Stratified by Time
From Symptom OnsetACS 337
Although the overall survivability benefits of reperfusion therapy are time dependent, the loss of efficacy caused by delay is
more pronounced with fibrinolysis than with PCI.75 The success of PCI in achieving TIMI-3 flow in the early hours after
STEMI does not change with time, whereas the ability of fibrinolytic therapy to achieve TIMI-3 flow decreases significantly
with increasing ischemic time.76 In this context, the choice of
reperfusion therapy for a STEMI patient when access to PCI
is delayed is a challenging one. The clinician has to weigh the

advantages of immediate fibrinolysis, which includes ease of
administration and potential to open the infarct-related artery
in a timely manner versus the limitations of fibrinolysis, which
include the risk of intracranial hemorrhage and bleeding and
the time sensitivity of the intervention’s efficacy to open the
infarct-related artery. Thus, total ischemic time is an important
variable in weighing the merits of delayed PCI versus immediate fibrinolysis.
In the 2010 AHA Guidelines for CPR and ECC,7 the recommendations were directed at patients in whom PCI could not
be accomplished within 90 minutes of first medical contact.
The 2015 ILCOR systematic review compared the relative
benefits of immediate fibrinolysis versus primary but delayed
PCI in treating STEMI patients, stratifying patients by time
from initial medical contact.
2015 Evidence Summary
In STEMI patients presenting less than 2 hours after symptom
onset in whom immediate PPCI will delay treatment 60 to 160
minutes compared with fibrinolysis, 2 RCTs (combined into
a single analysis) using an outcome of 30-day mortality77 and
1 RCT using an outcome of 5-year mortality showed greater
harm with delayed PPCI compared with fibrinolysis.78 No differences were found to incidence of reinfarction77 or severe
bleeding.79
For STEMI patients presenting 2 to 6 hours after symptom onset in whom PPCI will delay treatment 60 to 160 minutes compared with fibrinolysis, 2 RCTs using an outcome of
1-year mortality77 and 1 RCT using an outcome of 5-year mortality showed no benefit of delayed PPCI over fibrinolysis.78
There was also no difference in the incidence of reinfarction,77
but 1 RCT79 showed more severe bleeding with fibrinolysis as
compared with delayed PPCI.
In STEMI patients presenting 3 to 12 hours after symptom
onset in whom PPCI will delay treatment 60 to 120 minutes
as compared with fibrinolysis, 1 RCT80 using a 30-day mortality outcome showed that delayed PPCI conferred a benefit as
compared with immediate fibrinolysis.
A reanalysis of the raw data from 16 RCTs81 has suggested
that the acceptable fibrinolysis to PPCI delay varies depending on the patient’s baseline risk and delay to presentation. A
pragmatic simplification of the formula derived in the analysis
has been suggested in an editorial82 associated with the publication of the analysis: Patients older than 65 years and all
patients in Killip class greater than 1 should be treated with
PPCI. Patients older than 65 years in Killip class 1 should
have PPCI unless delay is greater than 35 minutes.
2015 Recommendations—Updated
The following recommendations are not in conflict with,
and do not replace, the 2013 ACC/AHA STEMI Guidelines,
which are endorsed by this ACS Writing Group. These 2015
Guidelines Update recommendations are derived from a different set of studies that examined the interval between symptom
onset and reperfusion, rather than the interval between first
medical contact and reperfusion. The symptom onset interval is appropriate to consider when time of symptom onset is
known. However, time from symptom onset may be difficult
to ascertain or may be unreliable. When time from symptom
onset is uncertain, it is appropriate to follow the ACC/AHA

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O’Connor et al   Part 9: Acute Coronary Syndromes   S489
STEMI Guidelines recommendation that PPCI is the preferred
reperfusion strategy when time from symptom onset is less
than 12 hours and time to PPCI from first medical contact
in these patients is anticipated to be less than 120 minutes.
Regardless of whether time of symptom onset is known, the
interval between first medical contact and reperfusion should
not exceed 120 minutes (Class I, LOE C-EO).
In STEMI patients presenting within 2 hours of symptom
onset, immediate fibrinolysis rather than PPCI may be considered when the expected delay to PPCI is more than 60 minutes
(Class IIb, LOE C-LD).
In STEMI patients presenting within 2 to 3 hours after
symptom onset, either immediate fibrinolysis or PPCI involving a possible delay of 60 to 120 minutes might be reasonable
(Class IIb, LOE C-LD).
In STEMI patients presenting within 3 to 12 hours after
symptom onset, performance of PPCI involving a possible
delay of up to 120 minutes may be considered rather than initial fibrinolysis (Class IIb, LOE C-LD).
It is acknowledged that fibrinolysis becomes significantly
less effective more than 6 hours after symptom onset, and thus
a longer delay to PPCI may be the better option for patients
more than 6 hours after symptom onset.
In STEMI patients, when delay from first medical contact
to PPCI is anticipated to exceed 120 minutes, a strategy of
immediate fibrinolysis followed by routine early (within 3 to
24 hours) angiography and PCI if indicated may be reasonable
for patients with STEMI (Class IIb, LOE B-R).

Reperfusion Therapy for STEMI in
Non–PCI-Capable HospitalsACS 332, ACS 334, ACS 779
The rapid restoration of perfusion in the infarct-related coronary artery, using either fibrinolytic therapy or PPCI, provides
the opportunity for an optimal outcome.
Fibrinolytic therapy unequivocally improves survival in
patients presenting with STEMI and has widespread availability.83 STEMI patients with contraindications to fibrinolytic
therapy and who are in cardiogenic shock are not appropriate
candidates for this form of reperfusion therapy.84 PPCI is superior to fibrinolytic therapy in the management of STEMI,85
because PPCI also improves survival rates and enhances other
important outcomes in the STEMI patient. However, this form
of reperfusion therapy is not widely available.
The superiority of PPCI over fibrinolytic therapy is not
absolute. For STEMI patients presenting to a non–PCI-­
capable hospital, the decision to administer fibrinolytic therapy at the initial facility as compared with immediate-transfer
PPCI requires consideration of several factors, including the
location of the MI, patient age, the duration of STEMI at time
of initial ED presentation, time required to complete transfer
for and performance of PPCI, and the abilities of the PPCI cardiologist and hospital.85 Furthermore, the hemodynamic status
of the patient is important; specifically, patients in cardiogenic
shock are most appropriately managed with PPCI.84
2015 Evidence Summary
Fibrinolysis Versus Transfer for PPCI
In a non–PCI-capable hospital, the choice of reperfusion
therapy in the STEMI patient is either immediate fibrinolytic

therapy or transfer for PPCI; the time required for transfer
of the patient to a PCI-capable hospital must be considered
in making the choice. Comparison studies showed benefit of
immediate transfer to a PCI center with respect to 30-day mortality, stroke, and/or reinfarction.80,86–92 There was no difference in major hemorrhage.88,91
Fibrinolysis and Routine Transfer for Angiography Versus
Immediate Transfer for PPCI
When immediate fibrinolysis in a non–PCI-capable hospital
followed by routine transfer for angiography was compared
with immediate transfer to a PCI center for PPCI, 3 studies
showed no benefit to 30-day mortality, stroke, and/or reinfarction and no difference in the rates of intracranial hemorrhage
or major bleeding.67,93,94
Fibrinolysis and Routine Transfer for Angiography Versus No
Routine Transfer: 30-Day Mortality
In patients who received a fibrinolytic agent for STEMI in a
non–PCI-capable hospital, studies comparing either routine
transfer for angiography at 3 to 6 hours and up to 24 hours
or no transfer except for ischemia-driven PCI (rescue PCI) in
the first 24 hours showed no benefit with respect to 30-day
mortality67,92,95–99 or 1-year mortality.67,95,96,99–101
Fibrinolysis and Routine Transfer for Angiography Versus
No Routine Transfer: Intracranial Hemorrhage or Major
Bleeding
In patients who received a fibrinolytic agent for STEMI in a
non–PCI-capable hospital, studies comparing either routine
transfer for angiography at 3 to 6 hours and up to 24 hours
or no transfer except for ischemia-driven PCI (rescue PCI)
in the first 24 hours demonstrated no difference in incidence
of intracranial hemorrhage,67,95–99 major bleeding,67,95–99 or
stroke.92,95,97,99
Fibrinolysis and Routine Transfer for Angiography Versus No
Routine Transfer: Reinfarction
When immediate fibrinolysis for STEMI was followed by routine transfer for angiography at 3 to 6 hours and up to 24 hours
as compared with no transfer except for ischemia-driven PCI
(rescue PCI) in the first 24 hours, a decrease in the rate of
reinfarction was demonstrated.67,92,95–99
2015 Recommendations—New
In adult patients presenting with STEMI in the ED of a non–
PCI-capable hospital, we recommend immediate transfer
without fibrinolysis from the initial facility to a PCI center
instead of immediate fibrinolysis at the initial hospital with
transfer only for ischemia-driven PCI (Class I, LOE B-R).
When STEMI patients cannot be transferred to a PCI-capable
hospital in a timely manner, fibrinolytic therapy with routine
transfer for angiography may be an acceptable alternative to
immediate transfer to PPCI (Class IIb, LOE C-LD).
When fibrinolytic therapy is administered to a STEMI
patient in a non–PCI-capable hospital, it may be reasonable to transport all postfibrinolysis patients for early routine angiography in the first 3 to 6 hours and up to 24 hours
rather than transport postfibrinolysis patients only when they
require ischemia-guided angiography (Class IIb, LOE B-R).
It is recognized that there may be practical and logistical circumstances, including geographic limitations, where transfer

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S490  Circulation  November 3, 2015
for angiography within 24 hours is difficult or impossible. In
these cases, the small but measurable decrease in reinfarction
rates may not justify a prolonged or difficult transfer.

Hospital Reperfusion Decisions After ROSC
PCI After ROSC With and Without ST
ElevationACS 340, ACS 885
In 2010, the ILCOR systematic review combined ST-elevation
and non–ST-elevation patients after ROSC. However, the
2010 AHA Guidelines for CPR and ECC did make separate recommendations for each of these distinct groups of
patients, recommending emergency coronary angiography
for ST-elevation patients after ROSC, while supporting the
consideration of coronary angiography for non–ST-elevation
patients after ROSC.
The 2015 ILCOR systematic review examined whether
immediate coronary angiography (angiography performed
within 24 hours after ROSC) for patients with and without ST
elevation after cardiac arrest improved outcomes.
2015 Evidence Summary
Evidence regarding the timing of coronary angiography
immediately after cardiac arrest (defined variously, but within
24 hours) is limited to observational studies.
Aggregated data from 15 studies of 3800 patients having
ST elevation on ECG after ROSC after cardiac arrest demonstrated a benefit of immediate coronary angiography, favoring

survival to hospital discharge,102–116 while 9 of these studies
enrolling a total of 2819 patients also demonstrated a benefit
favoring neurologically favorable outcomes.102–104,107,109–111,114,117
In patients without ST elevation on initial postarrest ECG,
2 studies demonstrated a benefit favoring improved survival
to hospital discharge and improved neurologically favorable outcome when patients received immediate coronary
angiography.102,107
In these studies, the decision to undertake the intervention was influenced by a variety of factors such as patient age,
duration of CPR, hemodynamic instability, presenting cardiac
rhythm, neurologic status upon hospital arrival, and perceived
likelihood of cardiac etiology.
2015 Recommendations—Updated
Coronary angiography should be performed emergently
(rather than later in the hospital stay or not at all) for OHCA
patients with suspected cardiac etiology of arrest and ST elevation on ECG (Class I, LOE B-NR).
Emergency coronary angiography is reasonable for select
(eg, electrically or hemodynamically unstable) adult patients
who are comatose after OHCA of suspected cardiac origin but
without ST elevation on ECG (Class IIa, LOE B-NR).
Coronary angiography is reasonable in post–cardiac arrest
patients where coronary angiography is indicated regardless
of whether the patient is comatose or awake (Class IIa, LOE
C-LD).

Disclosures
Part 9: Acute Coronary Syndromes: 2015 Guidelines Update Writing Group Disclosures
Writing Group
Member
Robert E. O’Connor

Employment

Research Grant

Other Research
Support

Speakers’ Bureau/
Honoraria

Expert Witness

Ownership
Interest

Consultant/
Advisory Board

Other

University of Virginia

None

None

None

None

None

None

None

Abdulaziz S. Al Ali

McMaster University

None

None

None

None

None

None

None

William J. Brady

University of Virginia

Siemens Medical
Diagnostics*

None

None

Medicolegal
consulting*

None

EvidenceCare†

None

Chris A.
Ghaemmaghami

University of Virginia

None

None

None

None

None

None

None

Cleveland Clinic

Astra Zeneca*

None

None

None

None

Astra Zeneca*;
Takeda
Pharmaceuticals†

None

Centre for Paramedic
Education and
Research

None

None

None

None

None

None

None

Mineral Springs
Hospital

None

None

None

None

None

American Heart
Association†

None

Venu Menon

Michelle Welsford

Consultant
Michael Shuster

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the
Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person
receives $10 000 or more during any 12-month period, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the
entity, or owns $10 000 or more of the fair market value of the entity. A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.
*Modest.
†Significant.

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O’Connor et al   Part 9: Acute Coronary Syndromes   S491

Appendix
2015 Guidelines Update: Part 9 Recommendations
Year Last
Reviewed

Topic

Recommendation

Comments

2015

Diagnostic Interventions in ACS

Prehospital 12-lead ECG should be acquired early for patients with possible ACS (Class I, LOE
B-NR).

new for 2015

2015

Diagnostic Interventions in ACS

Prehospital notification of the receiving hospital (if fibrinolysis is the likely reperfusion
strategy) and/or prehospital activation of the catheterization laboratory should occur for all
patients with a recognized STEMI on prehospital ECG (Class I, LOE B-NR).

updated for 2015

2015

Diagnostic Interventions in ACS

Because of high false-negative rates, we recommend that computer-assisted ECG
interpretation not be used as a sole means to diagnose STEMI (Class III: Harm, LOE B-NR).

new for 2015

2015

Diagnostic Interventions in ACS

We recommend that computer-assisted ECG interpretation may be used in conjunction with
physician or trained provider interpretation to recognize STEMI (Class IIb, LOE C-LD).

updated for 2015

2015

Diagnostic Interventions in ACS

While transmission of the prehospital ECG to the ED physician may improve PPV and
therapeutic decision-making regarding adult patients with suspected STEMI, if transmission
is not performed, it may be reasonable for trained non-physician ECG interpretation to be
used as the basis for decision-making, including activation of the catheterization laboratory,
administration of fibrinolysis, and selection of destination hospital (Class IIa, LOE B-NR).

new for 2015

2015

Diagnostic Interventions in ACS

We recommend against using hs-cTnT and cTnI alone measured at 0 and 2 hours (without
performing clinical risk stratification) to exclude the diagnosis of ACS (Class III: Harm, LOE
B-NR).

new for 2015

2015

Diagnostic Interventions in ACS

We recommend that hs-cTnI measurements that are less than the 99th percentile, measured
at 0 and 2 hours, may be used together with low-risk stratification (TIMI score of 0 or 1) to
predict a less than 1% chance of 30-day MACE (Class IIa, LOE B-NR).

new for 2015

2015

Diagnostic Interventions in ACS

We recommend that negative cTnI or cTnT measurements at 0 and between 3 and 6 hours
may be used together with very low-risk stratification (Vancouver score of 0 or North
American Chest Pain score of 0 and age less than 50 years) to predict a less than 1% chance
of 30-day MACE (Class IIa, LOE B-NR).

new for 2015

2015

Therapeutic Interventions in ACS

In patients with suspected STEMI intending to undergo PPCI, initiation of ADP inhibition may
be reasonable in either the prehospital or in-hospital setting (Class IIb, LOE C-LD).

new for 2015

2015

Therapeutic Interventions in ACS

We recommend that EMS systems that do not currently administer heparin to suspected
STEMI patients do not add this treatment, whereas those that do administer it may continue
their current practice (Class IIb, LOE B-NR).

new for 2015

2015

Therapeutic Interventions in ACS

In suspected STEMI patients for whom there is a planned PPCI reperfusion strategy,
administration of unfractionated heparin (UFH) can occur either in the prehospital or
in-hospital setting (Class IIb, LOE B-NR).

new for 2015

2015

Therapeutic Interventions in ACS

It may be reasonable to consider the prehospital administration of UFH in STEMI patients or
the prehospital administration of bivalirudin in STEMI patients who are at increased risk of
bleeding (Class IIb, LOE B-R).

new for 2015

2015

Therapeutic Interventions in ACS

In systems in which UFH is currently administered in the prehospital setting for patients with
suspected STEMI who are being transferred for PPCI, it is reasonable to consider prehospital
administration of enoxaparin as an alternative to UFH (Class IIa, LOE B-R).

updated for 2015

2015

Therapeutic Interventions in ACS

The usefulness of supplementary oxygen therapy has not been established in normoxic
patients. In the prehospital, ED, and hospital settings, the withholding of supplementary
oxygen therapy in normoxic patients with suspected or confirmed acute coronary syndrome
may be considered (Class IIb, LOE C-LD).

updated for 2015

2015

Therapeutic Interventions in ACS

Where prehospital fibrinolysis is available as part of a STEMI system of care, and in-hospital
fibrinolysis is the alternative treatment strategy, it is reasonable to administer prehospital
fibrinolysis when transport times are more than 30 minutes (Class IIa, LOE B-R).

updated for 2015

2015

Therapeutic Interventions in ACS

Where prehospital fibrinolysis is available as part of the STEMI system of care and direct
transport to a PCI center is available, prehospital triage and transport directly to a PCI center
may be preferred because of the small relative decrease in the incidence of intracranial
hemorrhage without evidence of mortality benefit to either therapy (Class IIb, LOE B-R).

new for 2015

2015

Therapeutic Interventions in ACS

In the treatment of patients with suspected STEMI, the combined application of fibrinolytic
therapy followed by immediate PCI (as contrasted with immediate PCI alone) is not
recommended. (Class III: Harm, LOE B-R).

new for 2015

2015

Therapeutic Interventions in ACS

If fibrinolytic therapy is provided, immediate transfer to a PCI center for cardiac angiography
within 3 to 24 hours may be considered (Class IIb, LOE C-LD).

new for 2015
(Continued )

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S492  Circulation  November 3, 2015
2015 Guidelines Update: Part 9 Recommendations, Continued
Year Last
Reviewed

Topic

Recommendation

Comments

2015

Therapeutic Interventions in ACS

Regardless of whether time of symptom onset is known, the interval between first medical
contact and reperfusion should not exceed 120 minutes (Class I, LOE C-EO).

new for 2015

2015

Therapeutic Interventions in ACS

In STEMI patients presenting within 2 hours of symptom onset, immediate fibrinolysis rather
than PPCI may be considered when the expected delay to PPCI is more than 60 minutes
(Class IIb, LOE C-LD).

updated for 2015

2015

Therapeutic Interventions in ACS

In STEMI patients presenting within 2 to 3 hours after symptom onset, either immediate
fibrinolysis or PPCI involving a possible delay of 60 to 120 minutes might be reasonable (Class
IIb, LOE C-LD).

updated for 2015

2015

Therapeutic Interventions in ACS

In STEMI patients presenting within 3 to 12 hours after symptom onset, performance of
PPCI involving a possible delay of up to 120 minutes may be considered rather than initial
fibrinolysis (Class IIb, LOE C-LD).

updated for 2015

2015

Therapeutic Interventions in ACS

In STEMI patients when long delays to PPCI are anticipated (more than 120 minutes), a
strategy of immediate fibrinolysis followed by routine early (within 3 to 24 hours) angiography
and PCI if indicated, is reasonable (Class IIb, LOE B-R).

updated for 2015

2015

Therapeutic Interventions in ACS

In adult patients presenting with STEMI in the ED of a non–PCI-capable hospital, we
recommend immediate transfer without fibrinolysis from the initial facility to a PCI center
instead of immediate fibrinolysis at the initial hospital with transfer only for ischemia-driven
PCI (Class I, LOE B-R).

new for 2015

2015

Therapeutic Interventions in ACS

When STEMI patients cannot be transferred to a PCI-capable hospital in a timely manner,
fibrinolytic therapy with routine transfer for angiography may be an acceptable alternative to
immediate transfer to PPCI (Class IIb, LOE C-LD).

new for 2015

2015

Therapeutic Interventions in ACS

When fibrinolytic therapy is administered to a STEMI patient in a non–PCI-capable hospital, it
may be reasonable to transport all postfibrinolysis patients for early routine angiography in the
first 3 to 6 hours and up to 24 hours rather than transport postfibrinolysis patients only when
they require ischemia-guided angiography (Class IIb, LOE B-R).

new for 2015

2015

Hospital Reperfusion Decisions
After ROSC

Coronary angiography should be performed emergently (rather than later in the hospital stay
or not at all) for OHCA patients with suspected cardiac etiology of arrest and ST elevation on
ECG (Class I, LOE B-NR).

updated for 2015

2015

Hospital Reperfusion Decisions
After ROSC

Emergency coronary angiography is reasonable for select (eg, electrically or hemodynamically
unstable) adult patients who are comatose after OHCA of suspected cardiac origin but without
ST elevation on ECG (Class IIa, LOE B-NR).

updated for 2015

2015

Hospital Reperfusion Decisions
After ROSC

Coronary angiography is reasonable in post–cardiac arrest patients where coronary
angiography is indicated regardless of whether the patient is comatose or awake (Class IIa,
LOE C-LD).

updated for 2015

The following recommendations were not reviewed in 2015. For more information, see the 2010 AHA Guidelines for CPR and ECC, “Part 10: Acute Coronary Syndromes.”
2010

Prehospital ECGs

If providers are not trained to interpret the 12-lead ECG, field transmission of the ECG or a
computer report to the receiving hospital is recommended (Class I, LOE B).

not reviewed in 2015

2010

Prehospital Fibrinolysis

It is strongly recommended that systems which administer fibrinolytics in the prehospital
setting include the following features: protocols using fibrinolytic checklists, 12-lead ECG
acquisition and interpretation, experience in advanced life support, communication with the
receiving institution, medical director with training and experience in STEMI management,
and continuous quality improvement (Class I, LOE C).

not reviewed in 2015

2010

Prehospital Triage and EMS
Hospital Destination

If PCI is the chosen method of reperfusion for the prehospital STEMI patient, it is reasonable
to transport patients directly to the nearest PCI facility, bypassing closer EDs as necessary,
in systems where time intervals between first medical contact and balloon times are <90
minutes and transport times are relatively short (ie, <30 minutes) (Class IIa, LOE B).

not reviewed in 2015

2010

Focused Assessment and ECG
Risk Stratification

This initial evaluation must be efficient because if the patient has STEMI, the goals of
reperfusion are to administer fibrinolytics within 30 minutes of arrival (30-minute interval
“door-todrug”) or to provide PCI within 90 minutes of arrival (90-minute interval “door-toballoon”) (Class I, LOE A).

not reviewed in 2015

2010

Cardiac Biomarkers

If biomarkers are initially negative within 6 hours of symptom onset, it is recommended that
biomarkers should be remeasured between 6 to 12 hours after symptom onset (Class I, LOE
A).

not reviewed in 2015

2010

STEMI

If the patient meets the criteria for fibrinolytic therapy, a door-to-needle time (initiation of
fibrinolytic agent) <30 minutes is recommended—the earlier the better (Class I, LOE A).

not reviewed in 2015

(Continued )

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O’Connor et al   Part 9: Acute Coronary Syndromes   S493
2015 Guidelines Update: Part 9 Recommendations, Continued
Year Last
Reviewed

Topic

Recommendation

Comments

2010

STEMI

Consultation delays therapy and is associated with increased hospital mortality rates (Class
III, LOE B).

not reviewed in 2015

2010

Indicators for Early Invasive
Strategies

An early invasive PCI strategy is indicated for patients with non–ST-elevation ACS who have
no serious comorbidity and who have coronary lesions amenable to PCI and an elevated risk
for clinical events (Class I, LOE A).

not reviewed in 2015

2010

Indicators for Early Invasive
Strategies

An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization)
is indicated in non–ST-elevation ACS patients who have refractory angina or hemodynamic
or electric instability (without serious comorbidities or contraindications to such procedures)
(Class I, LOE B).

not reviewed in 2015

2010

Indicators for Early Invasive
Strategies

In initially stabilized patients, an initially conservative (ie, a selectively invasive) strategy may
be considered as a treatment strategy for non–ST-elevation ACS patients (without serious
comorbidities or contraindications to such procedures) who have an elevated risk for clinical
events including those with abnormal troponin elevations (Class IIb, LOE B).

not reviewed in 2015

2010

The Chest Pain Unit Model

In patients with suspicion for ACS, normal initial biomarkers, and nonischemic ECG, chest
pain observation protocols may be recommended as a safe and effective strategy for
evaluating patients in the ED (Class I, LOE A).

not reviewed in 2015

2010

Fibrinolytics

If fibrinolysis is chosen for reperfusion, the ED physician should administer fibrinolytics to
eligible patients as early as possible according to a predetermined process of care developed
by the ED and cardiology staff (Class I, LOE A).

not reviewed in 2015

2010

Fibrinolytics

In fact, fibrinolytic therapy is generally not recommended for patients presenting between 12
and 24 hours after onset of symptoms based on the results of the LATE and EMERAS trials,
unless continuing ischemic pain is present with continuing ST-segment elevation (Class IIb,
LOE B).

not reviewed in 2015

2010

Fibrinolytics

Fibrinolytic therapy should not be administered (Class III, LOE B) to patients who present
greater than 24 hours after the onset of symptoms.

not reviewed in 2015

2010

Percutaneous Coronary
Intervention (PCI)

Coronary angioplasty with or without stent placement is the treatment of choice for the
management of STEMI when it can be performed effectively with a door-to-balloon time
<90 minutes by a skilled provider (performing >75 PCIs per year) at a skilled PCI facility
(performing >200 PCIs annually, of which at least 36 are primary PCI for STEMI)
(Class I, LOE A).

not reviewed in 2015

2010

PCI Following ROSC After
Cardiac Arrest

It is reasonable to include cardiac catheterization and coronary angiography in standardized
post– cardiac arrest protocols as part of an overall strategy to improve neurologically intact
survival in this patient group (Class IIa, LOE B).

not reviewed in 2015

2010

PCI Following ROSC After
Cardiac Arrest

Angiography and/or PCI need not preclude or delay other therapeutic strategies including
therapeutic hypothermia (Class IIa, LOE B).

not reviewed in 2015

2010

PCI Following ROSC After
Cardiac Arrest

A 12-lead ECG should be performed as soon as possible after ROSC (Class I, LOE A).

not reviewed in 2015

2010

PCI Versus Fibrinolytic Therapy

In summary, for patients presenting within 12 hours of symptom onset and
electrocardiographic findings consistent with STEMI, reperfusion should be initiated as soon
as possible – independent of the method chosen (Class I, LOE A).

not reviewed in 2015

2010

PCI Versus Fibrinolytic Therapy

Primary PCI performed at a high-volume center within 90 minutes of first medical contact
by an experienced operator that maintains an appropriate expert status is reasonable, as
it improves morbidity and mortality as compared with immediate fibrinolysis (<30 minutes
door-to-needle) (Class I, LOE A).

not reviewed in 2015

2010

PCI Versus Fibrinolytic Therapy

For those patients with a contraindication to fibrinolysis, PCI is recommended despite the
delay, rather than foregoing reperfusion therapy (Class I, LOE A).

not reviewed in 2015

2010

Clopidogrel

On the basis of these findings, providers should administer a loading dose of clopidogrel in
addition to standard care (aspirin, anticoagulants, and reperfusion) for patients determined to
have moderate- to high-risk non-ST-segment elevation ACS and STEMl (Class I, LOE A).

not reviewed in 2015

2010

Clopidogrel

It is reasonable to administer a 300-mg oral dose of clopidogrel to ED patients with suspected
ACS (without ECG or cardiac marker changes) who are unable to take aspirin because of
hypersensitivity or major gastrointestinal intolerance (Class IIa, LOE B).

not reviewed in 2015

2010

Clopidogrel

Providers should administer a 300-mg oral dose of clopidogrel to ED patients up to 75 years
of age with STEMI who receive aspirin, heparin, and fibrinolysis (Class I, LOE B).

not reviewed in 2015

2010

Prasugrel

Prasugrel (60 mg oral loading dose) may be substituted for clopidogrel after angiography in
patients determined to have non-ST-segment elevation ACS or STEMI who are more than 12
hours after symptom onset prior to planned PCI (Class IIa, LOE B).

not reviewed in 2015

(Continued )

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S494  Circulation  November 3, 2015
2015 Guidelines Update: Part 9 Recommendations, Continued
Year Last
Reviewed

Topic

Recommendation

Comments

2010

Prasugrel

There is no direct evidence for the use of prasugrel in the ED or prehospital settings. In
patients who are not at high risk for bleeding, administration of prasugrel (60-mg oral loading
dose) prior to angiography in patients determined to have STEMI ≤12 hours after the initial
symptoms may be substituted for administration of clopidogrel (Class IIa, LOE B).

not reviewed in 2015

2010

Initial EMS Care

Because aspirin should be administered as soon as possible after symptom onset to patients
with suspected ACS, it is reasonable for EMS dispatchers to instruct patients with no history
of aspirin allergy and without signs of active or recent gastrointestinal bleeding to chew an
aspirin (160 to 325 mg) while awaiting the arrival of EMS providers (Class IIa, LOE C).

not reviewed in 2015

2010

Initial EMS Care

If the patient is dyspneic, hypoxemic, or has obvious signs of heart failure, providers should
titrate therapy, based on monitoring of oxyhemoglobin saturation, to 94% (Class I, LOE C).

not reviewed in 2015

2010

Initial EMS Care

EMS providers should administer nonenteric aspirin (160 [Class I, LOE B] to 325 mg [Class I,
LOE C]).

not reviewed in 2015

2010

Initial EMS Care

Morphine is indicated in STEMI when chest discomfort is unresponsive to nitrates (Class I,
LOE C).

not reviewed in 2015

2010

Initial EMS Care

Morphine should be used with caution in unstable angina (UA)/NSTEMI due to an association
with increased mortality in a large registry (Class IIa, LOE C).

not reviewed in 2015

2010

Interfacility Transfer

These include patients who are ineligible for fibrinolytic therapy or who are in cardiogenic
shock (Class I, LOE C).

not reviewed in 2015

2010

Interfacility Transfer

Transfer of high-risk patients who have received primary reperfusion with fibrinolytic therapy
is reasonable (Class IIa, LOE B).

not reviewed in 2015

2010

TIMI Risk Score

These findings confirm the value of the TIMI risk score as a guide to therapeutic decisions
(Class IIa, LOE B).

not reviewed in 2015

2010

Indicators for Early Invasive
Strategies

The decision to implement an initial conservative (versus initial invasive) strategy in these
patients may be made by considering physician and patient preference (Class IIb, LOE C).

not reviewed in 2015

2010

Advanced Testing to Detect
Coronary Ischemia and CAD

For ED/CPU patients who are suspected of having ACS, have nonischemic ECG’s and negative
biomarkers, a noninvasive test for inducible myocardial ischemia or anatomic evaluation
of the coronary arteries (eg, computed tomography [CT] angiography, cardiac magnetic
resonance, myocardial perfusion imaging, stress echocardiography) can be useful in
identifying patients suitable for discharge from the ED (Class IIa, LOE B).

not reviewed in 2015

2010

Advanced Testing to Detect
Coronary Ischemia and CAD

MPS can also be used for risk stratification, especially in low- to intermediatelikelihood of
cardiac events according to traditional cardiac markers (Class IIa, LOE B).

not reviewed in 2015

2010

Advanced Testing to Detect
Coronary Ischemia and CAD

The use of MDCT angiography for selected low-risk patients can be useful to allow for safe
early discharge from the ED (Class IIa, LOE B).

not reviewed in 2015

2010

Safety of Discharge and Risk of
Major Adverse Cardiac Events
After Discharge From the ED/CPU

The use of inpatient-derived risk scoring systems are useful for prognosis (Class I, LOE A) but
are not recommended to identify patients who may be safely discharged from the ED (Class
III, LOE C).

not reviewed in 2015

2010

Aspirin and Nonsteroidal Antiinflammatory Drugs

Therefore, unless the patient has a known aspirin allergy or active gastrointestinal
hemorrhage, nonenteric aspirin should be given as soon as possible to all patients with
suspected ACS (Class I, LOE A).

not reviewed in 2015

2010

Aspirin and Nonsteroidal Antiinflammatory Drugs

NSAIDs (except for aspirin), both nonselective as well as COX-2 selective agents, should not
be administered during hospitalization for STEMI because of the increased risk of mortality,
reinfarction, hypertension, heart failure, and myocardial rupture associated with their use
(Class III, LOE C).

not reviewed in 2015

2010

Nitroglycerin (or Glyceryl
Trinitrate)

Patients with ischemic discomfort should receive up to 3 doses of sublingual or aerosol
nitroglycerin at 3- to 5-minute intervals until pain is relieved or low blood pressure limits its
use (Class I, LOE B).

not reviewed in 2015

2010

Nitroglycerin (or Glyceryl
Trinitrate)

The use of nitrates in patients with hypotension (SBP <90 mm Hg or ≥30 mm Hg below
baseline), extreme bradycardia (<50 bpm), or tachycardia in the absence of heart failure
(>100 bpm) and in patients with right ventricular infarction is contraindicated (Class III,
LOE C).

not reviewed in 2015

2010

Analgesia

Providers should administer analgesics, such as intravenous morphine, for chest discomfort
unresponsive to nitrates. Morphine is the preferred analgesic for patients with STEMI (Class
I, LOE C).

not reviewed in 2015

2010

β-Adrenergic Receptor Blockers

IV β-blocker therapy may be considered as reasonable in specific situations such as severe
hypertension or tachyarrhythmias in patients without contraindications (Class IIa, LOE B).

not reviewed in 2015
(Continued )

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O’Connor et al   Part 9: Acute Coronary Syndromes   S495
2015 Guidelines Update: Part 9 Recommendations, Continued
Year Last
Reviewed

Topic

Recommendation

Comments

2010

β-Adrenergic Receptor Blockers

In the absence of contraindications, PO β-blockers should be administered within the first 24
hours to patients with suspected ACS (Class I, LOE A).

not reviewed in 2015

2010

β-Adrenergic Receptor Blockers

It is reasonable to start oral β-blockers with low doses after the patient is stabilized prior to
discharge (Class IIa, LOE B).

not reviewed in 2015

2010

Treatment Recommendations
for UA/NSTEMI

For in-hospital patients with NSTEMI managed with a planned initial conservative approach,
either fondaparinux (Class IIa, LOE B) or enoxaparin (Class IIa, LOE A) are reasonable
alternatives to UFH or placebo.

not reviewed in 2015

2010

Treatment Recommendations
for UA/NSTEMI

For in-hospital patients with NSTEMI managed with a planned invasive approach, either
enoxaparin or UFH are reasonable choices (Class IIa, LOE A).

not reviewed in 2015

2010

Treatment Recommendations
for UA/NSTEMI

Fondaparinux may be used in the setting of PCI, but requires co-administration of UFH and
does not appear to offer an advantage over UFH alone (Class IIb, LOE A).

not reviewed in 2015

2010

Treatment Recommendations
for UA/NSTEMI

For in-hospital patients with NSTEMI and renal insufficiency, bivalirudin or UFH may be
considered (Class IIb, LOE A).

not reviewed in 2015

2010

Treatment Recommendations
for UA/NSTEMI

For in-hospital patients with NSTEMI and increased bleeding risk, where anticoagulant
therapy is not contraindicated, fondaparinux (Class IIa, LOE B) or bivalirudin (Class IIa, LOE A)
are reasonable and UFH may be considered (Class IIb, LOE C).

not reviewed in 2015

2010

Enoxaparin

For patients with STEMI managed with fibrinolysis in the hospital, it is reasonable to
administer enoxaparin instead of UFH (Class IIa, LOE A).

not reviewed in 2015

2010

Enoxaparin

In addition, for prehospital patients with STEMI managed with fibrinolysis, adjunctive
enoxaparin instead of UFH may be considered (Class IIb, LOE A).

not reviewed in 2015

2010

Enoxaparin

Patients initially treated with enoxaparin should not be switched to UFH and vice versa
because of increased risk of bleeding (Class III, LOE C).

not reviewed in 2015

2010

Enoxaparin

In younger patients <75 years the initial dose of enoxaparin is 30 mg IV bolus followed by
1 mg/kg SC every 12 hours (first SC dose shortly after the IV bolus) (Class IIb, LOE A).

not reviewed in 2015

2010

Enoxaparin

Patients ≥75 years may be treated with 0.75 mg/kg SC enoxaparin every 12 hours without an
initial IV bolus (Class IIb, LOE B).

not reviewed in 2015

2010

Enoxaparin

Patients with impaired renal function (creatinine clearance <30 mL/min) may be given
1 mg/kg enoxaparin SC once daily (Class IIb, LOE B).

not reviewed in 2015

2010

Enoxaparin

Patients with known impaired renal function may alternatively be managed with UFH (Class
IIb, LOE B).

not reviewed in 2015

2010

Fondaparinux

Fondaparinux (initially 2.5 mg IV followed by 2.5 mg SC once daily) may be considered
in the hospital for patients treated specifically with non-fibrin-specific thrombolytics (ie,
streptokinase), provided the creatinine is 3 mg/dL (Class IIb, LOE B).

not reviewed in 2015

2010

Unfractionated Heparin Versus
Low-Molecular-Weight Heparin
With PPCI in STEMI

For patients with STEMI undergoing contemporary PCI (ie, additional broad use of glycoprotein
IIb/IIIa inhibitors and a thienopyridine) enoxaparin may be considered a safe and effective
alternative to UFH (Class IIb, LOE B).

not reviewed in 2015

2010

Unfractionated Heparin Versus
Low-Molecular-Weight Heparin
With PPCI in STEMI

Patients initially treated with enoxaparin should not be switched to UFH and vice versa to
avoid increased risk of bleeding. Fondaparinux may be considered as an alternative to UFH,
however, there is an increased risk of catheter thrombi with fondaparinux alone. Additional
UFH (50 to 100 U/kg bolus) may help to avoid this complication (Class IIb, LOE B), but using
these two agents is not recommended over UFH alone.

not reviewed in 2015

2010

Unfractionated Heparin Versus
Low-Molecular-Weight Heparin
With PPCI in STEMI

For fondaparinux and enoxaparin it is necessary to adjust the dose in patients with renal
impairment. Bivalirudin may be considered as an alternative to UFH and GP IIb/IIIa inhibitors
(Class IIb, LOE A).

not reviewed in 2015

2010

ACE Inhibitors and ARBs in the
Hospital

Administration of an oral ACE inhibitor is recommended within the first 24 hours after onset of
symptoms in STEMI patients with pulmonary congestion or LV ejection fraction <40%, in the
absence of hypotension (SBP <100 mm Hg or ≥30 mm Hg below baseline) (Class I, LOE A).

not reviewed in 2015

2010

ACE Inhibitors and ARBs in the
Hospital

Oral ACE inhibitor therapy can also be useful for all other patients with AMI with or without
early reperfusion therapy (Class IIa, LOE B).

not reviewed in 2015

2010

ACE Inhibitors and ARBs in the
Hospital

IV administration of ACE inhibitors is contraindicated in the first 24 hours because of risk of
hypotension (Class III, LOE C).

not reviewed in 2015

2010

ACE Inhibitors in the Prehospital
Setting

In conclusion, although ACE inhibitors and ARBs have been shown to reduce long-term risk
of mortality in patients suffering an AMI, there is insufficient evidence to support the routine
initiation of ACE inhibitors and ARBs in the prehospital or ED setting (Class IIb, LOE C).

not reviewed in 2015

(Continued )

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S496  Circulation  November 3, 2015
2015 Guidelines Update: Part 9 Recommendations, Continued
Year Last
Reviewed

Topic

Recommendation

Comments

2010

HMG Coenzyme A Reductase
Inhibitors (Statins)

There is little data to suggest that this therapy should be initiated within the ED; however,
early initiation (within 24 hours of presentation) of statin therapy is recommended in patients
with an ACS or AMI (Class I, LOE C).

not reviewed in 2015

2010

HMG Coenzyme A Reductase
Inhibitors (Statins)

If patients are already on statin therapy, continue the therapy (Class IIb, LOE C).

not reviewed in 2015

2010

HMG Coenzyme A Reductase
Inhibitors (Statins)

Statins should not be discontinued during the index hospitalization unless contraindicated
(Class III, LOE C).

not reviewed in 2015

2010

HMG Coenzyme A Reductase
Inhibitors (Statins)

In conclusion, intensive (target LDL values optimally 70 mg/dL) statin treatment should be
initiated within the first 24 hours after onset of an ACS event (eg, immediately after hospital
admission) in all patients presenting with any form of ACS unless strictly contraindicated
(eg, by proven intolerance) (Class I, LOE A).

not reviewed in 2015

2010

Glucose-Insulin-Potassium

At this time there is little evidence to suggest that this intervention is helpful (Class IIb,
LOE C).

not reviewed in 2015

2010

Ventricular Rhythm Disturbances

the practice of prophylactic administration of lidocaine is not recommended (Class III, LOE A).

not reviewed in 2015

2010

Ventricular Rhythm Disturbances

Sotalol has not been adequately studied (Class IIb, LOE C).

not reviewed in 2015

2010

Ventricular Rhythm Disturbances

Amiodarone in a single RCT did not appear to improve survival in low doses and may increase
mortality in high doses when used early in patients with suspected myocardial infarction
(Class IIb, LOE C).

not reviewed in 2015

2010

Ventricular Rhythm Disturbances

prophylactic antiarrhythmics are not recommended for patients with suspected ACS or
myocardial infarction in the prehospital or ED (Class III, LOE A).

not reviewed in 2015

2010

Ventricular Rhythm Disturbances

Routine IV administration of β-blockers to patients without hemodynamic or electric
contraindications is associated with a reduced incidence of primary VF (Class IIb, LOE C).

not reviewed in 2015

2010

Ventricular Rhythm Disturbances

It is prudent clinical practice to maintain serum potassium >4 mEq/L and magnesium
>2 mEq/L (Class IIB, LOE A).

not reviewed in 2015

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Key Words: electrocardiogram ◼ fibrinolytics ◼ myocardial infarction
◼ ST-segment elevation ◼ unstable angina

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Part 9: Acute Coronary Syndromes: 2015 American Heart Association Guidelines Update
for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Robert E. O'Connor, Abdulaziz S. Al Ali, William J. Brady, Chris A. Ghaemmaghami, Venu
Menon, Michelle Welsford and Michael Shuster
Circulation. 2015;132:S483-S500
doi: 10.1161/CIR.0000000000000263
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